Type 1 Diabetes
Conditions
Brief summary
The primary objective of this study is to evaluate the safety and efficacy of the Medtronic hybrid closed-loop (HCL) system utilizing the proportional-integral-derivative algorithm with insulin feedback (PID-IFB) optimized to function in a hybrid mode with closed-loop control operating during the day and night.
Detailed description
Study participants will be asked to use the CGM and the study insulin pump provided for approximately 4 to 5 days prior to initiation of the HCL PID-IFB system in a hotel setting for another 4 to 5 days. All participants with diabetes and the parent/ guardian of participants \< 18 years of age will be asked to stay overnight in a hotel while the HCL PID-IFB system is on and to remain close to Stanford University during the day. For participants \> 18 years of age, designated remote monitors will be asked to receive alerts for low/ high glucose levels. Enrolled participants will be asked to complete evaluations to describe their user experience/ evaluation of the system.Each participant had a companion (parent/ legal guardian of participants \< 18 years of age, or the designate remote monitor for participants \> 18 years of age) who will consent to monitor the participant and complete an evaluation, but will not be considered enrolled in the study.
Interventions
DEVICEMedtronic Hybrid Closed-loop System - Android Platform
A continuous glucose sensor and insulin delivery system designed for continuous closed-loop control with the PID-IFB (proportional-integral-derivative insulin feed-back) algorithm using an Android controller.
DEVICEMedtronic Hybrid Closed-loop Integrated System
A fully integrated continuous glucose sensor and insulin delivery system designed for continuous closed-loop control with the PID-IFB (proportional-integral-derivative insulin feed-back) algorithm
Sponsors
Stanford University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Clinical diagnosis of type 1 diabetes (The diagnosis of type 1 diabetes is based on the investigator's judgment; C peptide level and antibody determinations are not needed.) * Daily insulin therapy for at least one year * Age between 14.0 to 40.0 years of age. The first 9 subjects (between all 3 centers) will be over 18 years old. * Subject has performed an average of at least 3 meter glucose readings per day in the preceding 2 weeks * Subject has used a downloadable insulin pump for at least 3 months * Subject comprehends written English * Female patients who are sexually active must be on acceptable method of contraception e.g. oral contraceptive pill, diaphragm, IUD * Female patients must have a negative urine pregnancy test * Informed Consent Form signed by the subject and/or parent and assent signed by the subject if \< age 18 * Parent/guardian (for subjects \< 18 years) and subject understand the study protocol and agree to comply with it. Both parents must sign if possible. * Total daily insulin requirement greater than 0.4 units/kg/day over the preceding two weeks. * No expectation that subject will be moving out of the area of the clinical center during the study. * Adults will need to be working within 20 minutes of our research staff during the day. * A person willing to fulfill the role of a remote monitor (such as parent, spouse or significant other).
Exclusion criteria
* Subject has a medical disorder that in the judgment of the investigator will affect the wearing of the devices or the completion of any aspect of the protocol * Diabetic ketoacidosis in the past month * History of seizure or loss of consciousness in the last 6 months * Subject has a respiratory condition such as asthma, treated with systemic or inhaled corticosteroids in the previous 6 months or cystic fibrosis * Subject has a history of any cardiac or vascular disorder such as myocardial infarction, unstable angina, coronary artery bypass surgery, coronary artery stenting, transient ischemic attack, cerebrovascular accident, angina, congestive heart failure, arrhythmia or thromboembolic disease * Subject has a history of liver or kidney disease (other than microalbuminuria) * Systolic blood pressure \> 140 mmHg on screening visit * Diastolic blood pressure \> 90 mmHg on screening visit * Subject has active Graves' disease * Subjects with inadequately treated thyroid disease or celiac disease * Subject has a neurologic disorder that in the judgment of the investigator will affect completion of the protocol * Either the subject or the subject's primary caregiver has received inpatient psychiatric treatment in the past 6 months * Subject has a history of diagnosed medical eating disorder * Subject has a history of known illicit drug abuse * Subject has a history of known prescription drug abuse * Subject has a history of current alcohol abuse * Subject has a history of visual impairment which would not allow subject to participate * Subject has an active skin condition that would affect sensor placement * Subject has adhesive allergies * Subjects requiring an intermediate or long-acting insulin (such as NPH, detemir or glargine) * Subjects requiring other anti-diabetic medications other than insulin (oral or injectable) * Current use of oral/inhaled glucocorticoids or other medications, which in the judgment of the investigator would be a contraindication to participation in the study * Subject is currently on beta blocker medication * Subject is currently participating in another investigational study (drug or device) * Subject is deemed by the investigator to be unwilling or unable to follow the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Count of Participants With no More Than One Meter Glucose Value <50 mg/dL and no Values <40 mg/dL, no More Than Two Episodes With Meter Glucose Values Remaining >300 mg/dL for More Than 1 Hour, and no Ketonemia, Seizures, or Loss of Consciousness | Up to 10 days | Our definition of a subject successfully participating in a cohort is: 1. No more than one meter glucose value \<50 mg/dL and no values \<40 mg/dL 2. No more than two episodes with meter glucose values remaining \>300 mg/dL for more than 1 hour that are unrelated to an infusion set failure 3. No ketonemia \>1.0 mmol/L, while the system is functional unless related to an intercurrent illness or infusion set failure 4. No seizures or loss of consciousness while system is on and functional |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Glucose Values, Fingerstick Glucose Meter Value, Adult Cohorts | Up to 10 days | Mean glucose values are reported as assessed by fingerstick glucose meter value. |
| Median Glucose Values, Fingerstick Glucose Meter Value, Adolescent Cohort | Up to 10 days | Median an glucose values are reported as assessed by fingerstick glucose meter value. |
| Percentage of Time Within Glucose Range of 70-180 mg/dL | Up to 10 days | — |
| Percentage of Fingerstick Meter Glucose Value Tests <70 mg/dL | Up to 10 days | — |
| Mean Glucose Values | Up to 10 days | Mean glucose values are reported as assessed by continuous glucose monitoring (CGM; subcutaneous sensor, day and night values). |
| Percentage of Time With Sensor Glucose Values <70 mg/DL, Adolescent Cohort | Up to 10 days | — |
| Percentage of Fingerstick Meter Glucose Value Tests >300 mg/dL, Adult Cohort - Medtronic Android Interface | Up to 10 days | — |
| Percentage of Fingerstick Meter Glucose Value Tests >300 mg/dL, Adult Cohort - Integrated System Interface and Adolescent Cohort | Up to 10 days | — |
| Percentage of Time With Sensor Glucose Values <70 mg/DL, Adult Cohorts | Up to 10 days | — |
Countries
United States
Participant flow
Recruitment details
Adults were recruited in the first 2 cohorts. Following analysis of the adult cohorts, adolescents were recruited in the third cohort.
Participants by arm
| Arm | Count |
|---|---|
| Adult Cohort In part 1, participants used the system with Android interface running the algorithm; in part 2, participants used the integrated system which ran the algorithm on the pump.
Medtronic Hybrid Closed-Loop System used by adults for five days in open-loop (algorithm off; sensor augmented pump) and five days in closed-loop (algorithm on). Algorithm was the PID-IFB (proportional-integral-derivative insulin feed-back) algorithm. | 9 |
| Adolescent Cohort Participants only participated in part 2, which used the integrated system which ran the algorithm on the pump.
Medtronic Hybrid Closed-Loop System used by adolescents for four days in open-loop (algorithm off; sensor augmented pump) and four days in closed-loop (algorithm on). Algorithm was the PID-IFB (proportional-integral-derivative insulin feed-back) algorithm. | 15 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Integrated Platform | Met stopping criteria | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Adult Cohort | Adolescent Cohort |
|---|---|---|---|
| Age, Customized 0-12 year | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized 13-17 years | 15 Participants | 0 Participants | 15 Participants |
| Age, Customized 18-64 years | 9 Participants | 9 Participants | 0 Participants |
| Age, Customized 65 year and older | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 17 Participants | 8 Participants | 9 Participants |
| Sex: Female, Male Male | 7 Participants | 1 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 9 | 1 / 15 |
| serious Total, serious adverse events | 0 / 9 | 0 / 15 |
Outcome results
Primary
Count of Participants With no More Than One Meter Glucose Value <50 mg/dL and no Values <40 mg/dL, no More Than Two Episodes With Meter Glucose Values Remaining >300 mg/dL for More Than 1 Hour, and no Ketonemia, Seizures, or Loss of Consciousness
Our definition of a subject successfully participating in a cohort is: 1. No more than one meter glucose value \<50 mg/dL and no values \<40 mg/dL 2. No more than two episodes with meter glucose values remaining \>300 mg/dL for more than 1 hour that are unrelated to an infusion set failure 3. No ketonemia \>1.0 mmol/L, while the system is functional unless related to an intercurrent illness or infusion set failure 4. No seizures or loss of consciousness while system is on and functional
Time frame: Up to 10 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adult Cohort - Medtronic Android Interface | Count of Participants With no More Than One Meter Glucose Value <50 mg/dL and no Values <40 mg/dL, no More Than Two Episodes With Meter Glucose Values Remaining >300 mg/dL for More Than 1 Hour, and no Ketonemia, Seizures, or Loss of Consciousness | 0 Participants |
| Adult Cohort - Integrated System Interface | Count of Participants With no More Than One Meter Glucose Value <50 mg/dL and no Values <40 mg/dL, no More Than Two Episodes With Meter Glucose Values Remaining >300 mg/dL for More Than 1 Hour, and no Ketonemia, Seizures, or Loss of Consciousness | 0 Participants |
| Adolescent Cohort | Count of Participants With no More Than One Meter Glucose Value <50 mg/dL and no Values <40 mg/dL, no More Than Two Episodes With Meter Glucose Values Remaining >300 mg/dL for More Than 1 Hour, and no Ketonemia, Seizures, or Loss of Consciousness | 1 Participants |
Secondary
Mean Glucose Values
Mean glucose values are reported as assessed by continuous glucose monitoring (CGM; subcutaneous sensor, day and night values).
Time frame: Up to 10 days
Population: Participants who completed the protocol were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adult Cohort - Medtronic Android Interface | Mean Glucose Values | Day (closed loop) | 156 mg/dL | Standard Deviation 14 |
| Adult Cohort - Medtronic Android Interface | Mean Glucose Values | Day (open loop) | 151 mg/dL | Standard Deviation 14 |
| Adult Cohort - Medtronic Android Interface | Mean Glucose Values | Night (closed loop) | 155 mg/dL | Standard Deviation 22 |
| Adult Cohort - Medtronic Android Interface | Mean Glucose Values | Night (open loop) | 156 mg/dL | Standard Deviation 26 |
| Adult Cohort - Integrated System Interface | Mean Glucose Values | Day (open loop) | 144 mg/dL | Standard Deviation 15 |
| Adult Cohort - Integrated System Interface | Mean Glucose Values | Night (closed loop) | 148 mg/dL | Standard Deviation 20 |
| Adult Cohort - Integrated System Interface | Mean Glucose Values | Night (open loop) | 142 mg/dL | Standard Deviation 18 |
| Adult Cohort - Integrated System Interface | Mean Glucose Values | Day (closed loop) | 152 mg/dL | Standard Deviation 14 |
| Adolescent Cohort | Mean Glucose Values | Night (closed loop) | 144 mg/dL | Standard Deviation 19 |
| Adolescent Cohort | Mean Glucose Values | Night (open loop) | 168 mg/dL | Standard Deviation 39 |
| Adolescent Cohort | Mean Glucose Values | Day (closed loop) | 153 mg/dL | Standard Deviation 17 |
| Adolescent Cohort | Mean Glucose Values | Day (open loop) | 171 mg/dL | Standard Deviation 30 |
Secondary
Mean Glucose Values, Fingerstick Glucose Meter Value, Adult Cohorts
Mean glucose values are reported as assessed by fingerstick glucose meter value.
Time frame: Up to 10 days
Population: Data are presented for adult cohorts only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adult Cohort - Medtronic Android Interface | Mean Glucose Values, Fingerstick Glucose Meter Value, Adult Cohorts | Open loop | 148 mg/dL | Standard Deviation 31 |
| Adult Cohort - Medtronic Android Interface | Mean Glucose Values, Fingerstick Glucose Meter Value, Adult Cohorts | Closed loop | 127 mg/dL | Standard Deviation 14 |
| Adult Cohort - Integrated System Interface | Mean Glucose Values, Fingerstick Glucose Meter Value, Adult Cohorts | Open loop | 164 mg/dL | Standard Deviation 41 |
| Adult Cohort - Integrated System Interface | Mean Glucose Values, Fingerstick Glucose Meter Value, Adult Cohorts | Closed loop | 151 mg/dL | Standard Deviation 36 |
Secondary
Median Glucose Values, Fingerstick Glucose Meter Value, Adolescent Cohort
Median an glucose values are reported as assessed by fingerstick glucose meter value.
Time frame: Up to 10 days
Population: Data are presented for the adolescent cohort only. Participants who completed the protocol were included in the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Adult Cohort - Medtronic Android Interface | Median Glucose Values, Fingerstick Glucose Meter Value, Adolescent Cohort | Open loop | 181 mg/dL |
| Adult Cohort - Medtronic Android Interface | Median Glucose Values, Fingerstick Glucose Meter Value, Adolescent Cohort | Closed loop | 132 mg/dL |
Secondary
Percentage of Fingerstick Meter Glucose Value Tests >300 mg/dL, Adult Cohort - Integrated System Interface and Adolescent Cohort
Time frame: Up to 10 days
Population: Data are presented for the Adult Cohort - Integrated System Interface and the Adolescent Cohort only. Participants who completed the protocol were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adult Cohort - Medtronic Android Interface | Percentage of Fingerstick Meter Glucose Value Tests >300 mg/dL, Adult Cohort - Integrated System Interface and Adolescent Cohort | Open loop | 3.0 percentage of readings | Standard Deviation 4.3 |
| Adult Cohort - Medtronic Android Interface | Percentage of Fingerstick Meter Glucose Value Tests >300 mg/dL, Adult Cohort - Integrated System Interface and Adolescent Cohort | Closed loop | 3.1 percentage of readings | Standard Deviation 2.5 |
| Adult Cohort - Integrated System Interface | Percentage of Fingerstick Meter Glucose Value Tests >300 mg/dL, Adult Cohort - Integrated System Interface and Adolescent Cohort | Open loop | 8.9 percentage of readings | Standard Deviation 9.8 |
| Adult Cohort - Integrated System Interface | Percentage of Fingerstick Meter Glucose Value Tests >300 mg/dL, Adult Cohort - Integrated System Interface and Adolescent Cohort | Closed loop | 6.7 percentage of readings | Standard Deviation 9.2 |
Secondary
Percentage of Fingerstick Meter Glucose Value Tests >300 mg/dL, Adult Cohort - Medtronic Android Interface
Time frame: Up to 10 days
Population: Data are presented for the Adult Cohort - Medtronic Android Interface only
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Adult Cohort - Medtronic Android Interface | Percentage of Fingerstick Meter Glucose Value Tests >300 mg/dL, Adult Cohort - Medtronic Android Interface | Open loop | 0.0 percentage of readings |
| Adult Cohort - Medtronic Android Interface | Percentage of Fingerstick Meter Glucose Value Tests >300 mg/dL, Adult Cohort - Medtronic Android Interface | Closed loop | 0.7 percentage of readings |
Secondary
Percentage of Fingerstick Meter Glucose Value Tests <70 mg/dL
Time frame: Up to 10 days
Population: Participants who completed the protocol were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adult Cohort - Medtronic Android Interface | Percentage of Fingerstick Meter Glucose Value Tests <70 mg/dL | Open loop | 4.7 percentage of tests | Standard Deviation 5.1 |
| Adult Cohort - Medtronic Android Interface | Percentage of Fingerstick Meter Glucose Value Tests <70 mg/dL | Closed loop | 1.4 percentage of tests | Standard Deviation 1.7 |
| Adult Cohort - Integrated System Interface | Percentage of Fingerstick Meter Glucose Value Tests <70 mg/dL | Open loop | 13.0 percentage of tests | Standard Deviation 9.7 |
| Adult Cohort - Integrated System Interface | Percentage of Fingerstick Meter Glucose Value Tests <70 mg/dL | Closed loop | 7.6 percentage of tests | Standard Deviation 2.9 |
| Adolescent Cohort | Percentage of Fingerstick Meter Glucose Value Tests <70 mg/dL | Open loop | 11.7 percentage of tests | Standard Deviation 9.9 |
| Adolescent Cohort | Percentage of Fingerstick Meter Glucose Value Tests <70 mg/dL | Closed loop | 13.5 percentage of tests | Standard Deviation 13.9 |
Secondary
Percentage of Time Within Glucose Range of 70-180 mg/dL
Time frame: Up to 10 days
Population: Participants who completed the protocol were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adult Cohort - Medtronic Android Interface | Percentage of Time Within Glucose Range of 70-180 mg/dL | Open loop | 71.9 percentage of time in range | Standard Deviation 10.6 |
| Adult Cohort - Medtronic Android Interface | Percentage of Time Within Glucose Range of 70-180 mg/dL | Closed loop | 71.0 percentage of time in range | Standard Deviation 12.4 |
| Adult Cohort - Integrated System Interface | Percentage of Time Within Glucose Range of 70-180 mg/dL | Open loop | 67.7 percentage of time in range | Standard Deviation 8.1 |
| Adult Cohort - Integrated System Interface | Percentage of Time Within Glucose Range of 70-180 mg/dL | Closed loop | 71.8 percentage of time in range | Standard Deviation 12.5 |
| Adolescent Cohort | Percentage of Time Within Glucose Range of 70-180 mg/dL | Open loop | 55.2 percentage of time in range | Standard Deviation 14.2 |
| Adolescent Cohort | Percentage of Time Within Glucose Range of 70-180 mg/dL | Closed loop | 69.8 percentage of time in range | Standard Deviation 9.7 |
Secondary
Percentage of Time With Sensor Glucose Values <70 mg/DL, Adolescent Cohort
Time frame: Up to 10 days
Population: Data are presented for the adolescent cohort only. Participants who completed the protocol were included in the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Adult Cohort - Medtronic Android Interface | Percentage of Time With Sensor Glucose Values <70 mg/DL, Adolescent Cohort | Day (open loop) | 2.7 percentage of time |
| Adult Cohort - Medtronic Android Interface | Percentage of Time With Sensor Glucose Values <70 mg/DL, Adolescent Cohort | Day (closed loop) | 2.5 percentage of time |
| Adult Cohort - Medtronic Android Interface | Percentage of Time With Sensor Glucose Values <70 mg/DL, Adolescent Cohort | Night (open loop) | 2.5 percentage of time |
| Adult Cohort - Medtronic Android Interface | Percentage of Time With Sensor Glucose Values <70 mg/DL, Adolescent Cohort | Night (closed loop) | 0.7 percentage of time |
Secondary
Percentage of Time With Sensor Glucose Values <70 mg/DL, Adult Cohorts
Time frame: Up to 10 days
Population: Data are presented for adult cohorts only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adult Cohort - Medtronic Android Interface | Percentage of Time With Sensor Glucose Values <70 mg/DL, Adult Cohorts | Day (open loop) | 2.7 percentage of time | Standard Deviation 1.3 |
| Adult Cohort - Medtronic Android Interface | Percentage of Time With Sensor Glucose Values <70 mg/DL, Adult Cohorts | Day (closed loop) | 1.4 percentage of time | Standard Deviation 1.8 |
| Adult Cohort - Medtronic Android Interface | Percentage of Time With Sensor Glucose Values <70 mg/DL, Adult Cohorts | Night (open loop) | 3.5 percentage of time | Standard Deviation 4.3 |
| Adult Cohort - Medtronic Android Interface | Percentage of Time With Sensor Glucose Values <70 mg/DL, Adult Cohorts | Night (closed loop) | 1.9 percentage of time | Standard Deviation 3.4 |
| Adult Cohort - Integrated System Interface | Percentage of Time With Sensor Glucose Values <70 mg/DL, Adult Cohorts | Night (closed loop) | 1.2 percentage of time | Standard Deviation 1.7 |
| Adult Cohort - Integrated System Interface | Percentage of Time With Sensor Glucose Values <70 mg/DL, Adult Cohorts | Day (open loop) | 7.6 percentage of time | Standard Deviation 5.4 |
| Adult Cohort - Integrated System Interface | Percentage of Time With Sensor Glucose Values <70 mg/DL, Adult Cohorts | Night (open loop) | 8.2 percentage of time | Standard Deviation 8.7 |
| Adult Cohort - Integrated System Interface | Percentage of Time With Sensor Glucose Values <70 mg/DL, Adult Cohorts | Day (closed loop) | 2.0 percentage of time | Standard Deviation 1.4 |